2.9A ). Microvilli are small (typically 1 to 3 µm in length), nonmotile projections of the apical plasma membrane that serve to increase surface area. They are commonly located on cells that must transport large quantities of ions, water, and molecules (e.g., epithelial cells lining the small intestine and cells of the renal proximal tubule). The core of the microvilli is composed of actin filaments and a number of accessory proteins. This actin core is connected to the cytoskeleton of the cell via the terminal web (a network of actin fibers at
Epithelialcelltightjunctions(alsocalledzonula occludens)arecomposedofseveralintegralmembraneproteins,includingoccludins, claudins, andseveralmembersoftheimmunoglobulinsuperfamily(e.g.,thejunctional adhesion molecule [JAM]).Occludinsandclaudinsaretransmembraneproteinsthatspanthemembraneofonecellandlinktotheextracellularportionofthesamemoleculeintheadjacentcell.Cytoplasmiclinkerproteins(e.g.,tightjunctionprotein[ZO-1,ZO-2,andZO-3])thenlinkthemembranespanningproteinstothecytoskeletonofthecell.
Ofthesejunctionalproteins,claudinsappeartobeimportantindeterminingthepermeabilitycharacteristicsofthetightjunction,especiallywithregardtocationsandanions.Todate,27mammalianclaudingeneshavebeenidentified,and26arefoundinthehumangenome(thegeneforclaudin13isnotfoundinhumans).Certainclaudinsserveasbarrierproteinsthatrestrictthemovementofionsthroughthetightjunction,whereasothersforma“pore”thatfacilitatesthemovementofionsthroughthejunction.Thusthepermeabilitycharacteristicsofthetightjunctionofanepitheliumaredeterminedbythecomplementofclaudinsexpressedbythecell.Forexample,theproximaltubuleofthekidneyistermeda“leaky”epithelium,inwhichwaterandsolutes(e.g.,Na+)movethroughthejunction.Claudin4andclaudin10areexpressedinthetightjunctionofproximaltubulecells.Incontrast,thecollectingductofthekidneyisconsidereda“tight”epithelium,withrestrictedmovementofionsthroughthetightjunction.Collectingductcellsexpressclaudins3,4,7,8,10,and18.
Thefunctionofclaudinscanberegulatedatseverallevels,includinggeneexpression,posttranslationalmodification,interactionswithcytoplasmicscaffoldingproteins,andinteractionswithotherclaudinsinthesamemembrane(cis-interaction),aswellaswithclaudinsofadjacentcells(trans-interaction).ThemineralocorticoidhormonealdosteronestimulatesNa+ reabsorptionbydistalsegmentsoftherenalnephron(see ).Inadditiontothehormone’seffectonNa+ transportersinthecell,aldosteronealsoupregulatesexpressionofclaudin8inthetightjunction.Theincreasedexpressionofclaudin8reducestheabilityofNa+ topermeatethetightjunction,whichthenreducesthebackwardsleakofNa+ fromtheinterstitiumintothetubulelumen,therebyallowingmoreefficientNa+ reabsorptionbytheepithelium.